Interactions between osteoclasts, osteoblasts and immune cells: implications for the pathogenesis of bone loss in thalassemia.

Bone is an active tissue constantly being remodeled and changing metabolically through the balanced activity of osteoclasts, osteoblasts and osteocytes. Recent data have revealed the role of immune system to regulate bone cells and participate in the pathogenesis of several bone disorders. The RANK/RANKL/OPG system and the Wnt signaling are crucial pathways for the differentiation and function of osteoclasts and osteoblasts. Osteopenia and osteoporosis represent painful complications of thalassemia. Several factors that are responsible for bone loss in thalassemia act through the activation of osteoclasts and/or the inhibition of osteoblasts. Alterations in the RANKL/OPG ratio and increased serum levels of Wnt antagonists are present in thalassemic patients with osteoporosis. This review summarizes all available data for the interactions between bone and immune cells and their possible implications for the pathogenesis of bone loss in thalassemia. Through the understanding of the molecular pathways that are responsible for bone destruction in these patients we will be able to produce novel agents targeting these pathways and thus improve the management of osteoporosis in thalassemia.